ABSTRACT
Objective: To prepare tetrahydropalmatine (THP) and β-cyclodextrin (β-CD) and its derivatives inclusion complexes (HP-β-CD, DM-β-CD, and TM-β-CD and explore their inclusion behavior and properties. Methods: The inclusion complexes of THP with β-CD, HP-β-CD, DM-β-CD, and TM-β-CD were prepared by saturated solution. The inclusion ratio and stability constant of inclusion complexes were determined with the Job plot and UV-vis spectroscopy. The THP/CDs complexes were characterized and determinated by means of XRD, TG, and SEM. The molecular simulation was processed to investigate the inclusion behavior of THP and different CDs. The water solubility of the inclusion complexes was measured and the stability test was conducted in the simulated human gastric juice and intestinal fluid environment. Results: Job plot and UV-vis spectroscopy showed that inclusion ratio of host-guest inclusion complexes was 1:1. Molecular docking showed that the entire THP entered the macrophage port and run through the cavities of β-CD and DM-β-CD, with the two aromatic rings located at the large and small mouth, respectively. For HP-β-CD and TM-β-CD, the two nitrogen heterocycle of THP were “V” shaped inlaid into the CD cavity, and both aromatic rings were located at the large end of the CDs. Conclusion: The solubility of tetrahydropalmatine was increased from 0.30 mg/mL to 1.60, 3.40, 9.13, and 4.02 mg/mL for β-CD, HP-β-CD, DM-β-CD, and TM-β-CD, respectively. The thermal stability and biological environment stability had been significantly improved.
ABSTRACT
This study was aimed to evaluate the in vitro complexation nature and strength of complex which may be formed due to interaction between Amoxicillin and Calcium chloride (CaCl2). The interaction of Amoxicillin and Calcium chloride (fused) has been studied in aqueous systems at a fixed temperature (37 ± 0.5) °C and under different pH (pH 2.4 and pH 7.4) by using some physical methods as spectral observation, Job’s method of continuous variation, Ardon’s method. From spectrophotometric study, Amoxicillin gives a sharp peak at 272 nm when Calcium chloride mixed with Amoxicillin in 1:1 ratio the intensity of the peak of Amoxicillin change remarkably due to interaction. The jobs plot was obtained by plotting absorbance difference against the mole fraction of the each drug at pH 2.4 and pH 7.4. Amoxicillin forms strong 1:1 complex with Calcium chloride and reverse V Shaped curves indicate the formation of 1:1 complexes of Amoxicillin with Calcium chloride. These may indicate strong kinetics of complexation between Amoxicillin with Calcium chloride. The value of stability constant for the complexation of Amoxicillin with calcium chloride at pH 2.4 and pH 7.4 were obtained from the spectral data using Ardon’s plot. The value of stability constant for the drug-metal system at pH 2.4 and pH 7.4 are 5.54 and 6.67 respectively. At pH 2.4 it is found that Amoxicillin form relatively stable complex with Calcium chloride (stability constant 6.67) is high in comparison to pH 7.4. It can therefore be concluded that a careful consideration is needed during concurrent administration of Amoxicillin with Calcium chloride.